Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction

Aging is a complex physiological process that poses considerable conundrums to rapidly aging societies. For example, the risk of dying from cardiovascular diseases and/or cancer steadily declines for people after their 60s, and other causes of death predominate for seniors older than 80 years of age. Thus, physiological aging presents numerous unanswered questions, particularly with regard to changing metabolic patterns. Urine proteomics analysis is becoming a non-invasive and reproducible diagnostic method. We investigated the urine proteomes in healthy elderly people to determine which metabolic processes were weakened or strengthened in aging humans. Urine samples from 37 healthy volunteers aged 19–90 years (19 men, 18 women) were analyzed for protein expression by liquid chromatography–tandem mass spectrometry. This generated a list of 19 proteins that were differentially expressed in different age groups (young, intermediate, and old age). In particular, the oldest group showed protein changes reflective of altered extracellular matrix turnover and declining immune function, in which changes corresponded to reported changes in cardiovascular tissue remodeling and immune disorders in the elderly. Thus, urinary proteome changes in the elderly appear to reflect the physiological processes of aging and are particularly clearly represented in the circulatory and immune systems. Detailed identification of “protein trails” creates a more global picture of metabolic changes that occur in the elderly.     

The Ginkgo biloba extract (GbE) protects the kidney from damage produced by a single and low dose of carbon tetrachloride in adult male rats

Gingko biloba leaves have been used as herbal medicine in China for 5000 years, and the standardized leaf extract (GB-STE) has some beneficial effects in the treatment of age-related, cardiovascular, and neurological diseases. The aim of this study was to investigate the renoprotective effects of the Gingko biloba extract (GbE) against the toxicity of a single and relatively low dose of carbon tetrachloride (CCl₄). In male adult Wistar rats, we determined the urine flux, the concentration of total proteins in urine, the concentration of glucose in urine, and the concentration of malondialdehyde (MDA) in renal cortex as well as two markers of renal function (clearance of inulin and p-aminohippurate); we also compared the histological lesions caused by CCl₄. Carbon tetrachloride increased the urinary concentration of total proteins, and the renal concentration of MDA; however, it did not modify the urine flux, urinary concentration of glucose, nor the inuline or the p-aminohipurate clearances. Morphologically, CCl₄ generated some tubular damage that was more intense in the inner cortex of kidneys. The GbE extract counteracted the effects of CCl₄ on the concentration of total proteins in urine, the concentration of renal MDA, and the renal histological changes. In conclusion the main toxic effects produced by CCl₄ were prevented by the GbE, probably due to their antioxidant properties and the inhibition of the main P450 isoenzyme (CYP2E1) that metabolize CCl₄.     

连云港市1995～2005年碘缺乏病防治10年效果评价

目的全面了解连云港市碘缺乏病防治状况,评价防治效果。方法按照《全国IDD防治监测方案》和《江苏省市、县消除碘缺乏病考核评审方案》,使用PPS法抽样,在全市范围内抽取1 000多名8~10岁学生进行甲状腺肿大率调查和尿碘含量检测,以及学生家庭食用盐进行碘含量测定,并抽取五年级学生和学校附近家庭主妇进行IDD知识问卷调查。结果碘盐覆盖率从1995年的59.10%上升到2005年的92.82%,甲状腺肿大率从1995年的43.78%下降到2005年的2.02%,尿碘中位数从1995年的71.25μg/L上升到2005年的170.40μg/L。结论综合病情和各项监测指标,我市推行"全民食用加碘盐防治碘缺乏病"措施10年后,达到了消除碘缺乏病的目标。     

临床尿液常规检验分析前质量控制对策与效果探析

目的：探讨临床尿液常规检验分析前质量控制对策,并对其对策的应用效果进行分析。方法以2013年9月-2014年8月该院收治的肾内科患者共200例作为研究的对象,随机将其分成实验组和对照组,每组各100例,对照组患者给予常规的临床尿液检查控制,实验组患者在临床尿液常规检验分析前给予质量控制。结果该实验中所有的标本均完成了检查,检查结果可靠。且通过我们的质量控制,实验组的100例患者仅出现2例与显微镜检查不符的情况,占2%;有98%与患者的尿显微镜检查结果相符,对照组患者出现11例与显微镜检查不符的情况,占11%,有89%与患者的尿显微镜检查结果相符,差异存在统计学意义(P<0.05)。结论在临床尿液常规检验中要积极进行分析前的质量控制,以改善尿常规的检查效果,使其尿常规检查结果具有较好的准确率,更好地对临床疾病进行诊治。     

血清胱抑素C、尿微量白蛋白/肌酐比值联合测定在老年2型糖尿病早期肾病诊断的价值

目的:探讨血清胱抑素C(Cys-C)、尿微量白蛋白(UAlb)/肌酐(Cr)水平的联合测定对老年2型糖尿病肾病(DN)的诊断价值。方法:入选老年2型糖尿病(T2DM)患者120例,根据内生肌酐清除率(Ccr)分三组:肾功能正常组,Ccr≥90 m L/min,40例;肾功能轻度减退组,60 m L/min≤Ccr90 m L/min,40例;肾功能重度减退组,Ccr60 m L/min,40例。并以40例健康体检者作为对照组,四组年龄均≥60岁。用免疫比浊法测定各组Cys-C、UAlb/Cr比值。结果:肾功能轻度减退组和肾功能重度减退组患者Cys-C及UAlb/Cr水平与肾功能正常组及对照组比较明显升高,且差异具有统计学意义(P0.05)。肾功能轻度减退组Cys-C、UAlb/Cr水平明显低于肾功能重度减退组,比较差异有统计学意义(P0.05);且Cys-C及UAlb/Cr比值水平,均与血Cr水平成正相关。结论:联合测定Cys-C及UAlb/Cr比值对老年2型糖尿病患者早期肾功能损伤评价,具有十分重要价值,有利于早期干预及治疗。     

尿百草枯与动脉血乳酸浓度对急性百草枯中毒的预后评估

目的：观察急性百草枯中毒（APP）患者入院时尿百草枯（PQ）浓度与动脉血乳酸（Lac）浓度变化,探讨APP 患者预后特异度和敏感度较高的监测指标。方法收集我院急诊内科2012年1月－2015年1月 APP 患者142例的临床资料,根据中毒后30 d 是否死亡分为死亡组与存活组,记录入院时尿 PQ 浓度和血 Lac 浓度,通过 ROC 曲线评估其对 APP 预后的诊断价值。结果死亡组患者入院时尿 PQ 浓度和血 Lac 浓度明显高于存活组（P ＜0．05）;两者对 APP 患者死亡预测的 ROC 曲线下面积（AUC）显示,尿 PQ 浓度的 AUC 为0．843,截断值为50．12 mg／L,敏感度为78．6％,特异度为88．5％,Youden 指数0．671;血 Lac 浓度的 AUC 为0．782,截断值为3．76 mmol／L,敏感度为85．4％,特异度为76．7％,Youden 指数0．621。结论入院时尿 PQ 浓度（≥50．12 mg／L）和（或）血 Lac 浓度（≥3．76 mmol／L）可作为预测 APP 患者预后的参考指标。     

Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease

BackgroundUbiquitin-52 amino acid fusion protein (UbA52) is an important factor in the pathogenesis of diabetic kidney disease (DKD) and has been suggested a potential marker in the disease. However, whether upregulation of UbA52 marks early kidney injury in T2DM mellitus (T2DM) patients remains unclear. In this study, we examine the diagnostic value of UbA52 as a biomarker in predicting early diabetic kidney disease (DKD) in T2DM patients.MethodsWe used two-step ELISA to test UbA52 level in urine of 3 defined patient groups. Samples from T2DM patients without albuminuria or diabetic retinopathy (DM-WNP; n = 30), T2DM patients with albuminuria and diabetic retinopathy, excluding other renal diseases clinically (DM-NP; n = 30) and healthy controls (n = 30) were analyzed. Spearman's correlation analysis and multiple linear regression model were used to analyze the correlation of urinary UbA52 level with laboratory results regarding kidney function. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of UbA52 in predicting T2DM and early DKD.ResultsUrinary UbA52 level in DM-NP group was 1.75 times and 2.71 times higher than in DN-WNP (p = 0.004) and normal control group (p < 0.001), respectively. The level of urinary UbA52 correlated significantly with serum creatinine (r = 0.468, p < 0.001), GFR (r = −0.300, p = 0.004) and proteinuria (r = 0.484, p < 0.001). Multiple linear regression analysis showed that proteinuria level was independently associated with urinary UbA52 level (β = 0.833, p < 0.001). The area under the ROC of urinary UbA52 in diagnosing T2DM and DKD was 0.751 and 0.755, respectively.ConclusionThe level of urinary UbA52 increased significantly in T2DM patients with DKD. The level of proteinuria is independently associated with urinary UbA52 level. Urinary UbA52 could serve as an early marker in the diagnosis of DKD.ClinicalTrials.gov Identifier: NCT02204280.     

Urinary Nucleic Acid TSPAN13-to-S100A9 Ratio as a Diagnostic Marker in Prostate Cancer

The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.     

Predictors of urinary levels of 2,4-dichlorophenoxyacetic acid, 3,5,6-trichloro-2-pyridinol, 3-phenoxybenzoic acid,and pentachlorophenol in 121 adults in Ohio

Limited data exist on the driving factors that influence the non-occupational exposures of adults to pesticides using urinary biomonitoring. In this work, the objectives were to quantify the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol (TCP), 3-phenoxybenzoic acid (3-PBA), and pentachlorophenol (PCP) in 121 adults over a 48-h monitoring period and to examine the associations between selected sociodemographic and lifestyle factors and urinary levels of each pesticide biomarker. Adults, ages 20–49 years old, were recruited from six counties in Ohio (OH) in 2001. The participants collected 4–6 spot urine samples and completed questionnaires and diaries at home over a 48-h monitoring period. Urine samples were analyzed for 2,4-D, TCP, 3-PBA, and PCP by gas chromatography/mass spectrometry. Multiple regression modeling was used to determine the impact of selected sociodemographic and lifestyle factors on the log-transformed (ln) levels of each pesticide biomarker in adults. The pesticide biomarkers were detected in ≥89% of the urine samples, except for 3-PBA (66%). Median urinary levels of 2,4-D, TCP, 3-PBA, and PCP were 0.7, 3.4, 0.3, and 0.5 ng/mL, respectively. Results showed that 48-h sweet/salty snack consumption, 48-h time spend outside at home, and ln(creatinine) levels were significant predictors (p < 0.05), and race was a marginally significant predictor (p = 0.093) of the adults’ ln(urinary 2,4-D) concentrations. Strong predictors (p < 0.05) of the adults’ ln(urinary TCP) concentrations were urbanicity, employment status, sampling season, and ln(creatinine) levels. For 3-PBA, sampling season, pet ownership and removal of shoes before entering the home were significant predictors (p < 0.05) of the adults’ ln(urinary 3-PBA) levels. Finally for PCP, removal of shoes before entering the home and ln(creatinine) levels were significant predictors (p < 0.05), and pet ownership was a marginally significant predictor (p = 0.056) of the adults’ ln(urinary PCP) concentrations. In conclusion, specific sociodemographic and lifestyle factors were identified that increased the exposures of these adults to several different pesticides in their daily environments.     

泌尿系感染患者病原菌分布及药敏特征分析

目的分析泌尿系统感染病原菌分布及耐药特征,为临床合理使用抗菌药物提供依据。方法对2011-2012年3 879例尿路感染患者尿培养中分离出的病原菌,采用法国生物梅里埃公司VITEK-2全自动细菌鉴定药敏仪和GN鉴定卡进行菌株鉴定,AST-GN16药敏卡进行药敏试验,并对产ESBLs耐药表型的菌株用双纸片法进行确证。结果 3 879份尿培养标本检出病原菌1 066株,检出率为27.5%;其中革兰阴性菌765株占71.8%,革兰阳性菌215株占20.2%,真菌86株占8.0%,检出率最高的前4位病原菌依次为大肠埃希菌、屎肠球菌、肺炎克雷伯菌和粪肠球菌,分别占51.3%、11.3%、7.6%和5.9%;大肠埃希菌和肺炎克雷伯菌产ESBLs检出率分别为64.4%、64.2%,产ESBLs大肠埃希菌和肺炎克雷伯菌对亚胺培南、美罗培南敏感率较高,>99.0%,对其余抗菌药物敏感率较低,<78.0%;肠球菌属耐药增长迅速。结论泌尿系统感染病原菌以革兰阴性菌为主,大肠埃希菌是主要病原菌,产ESBLs菌检出率较高且呈多药耐药特征,临床上应根据药敏结果合理用药。